Anti-inflammatory effects of vicenin-2 and scolymoside in vitro and in vivo.

Objective: Two structurally related flavonoids found in Cyclopia subternata, namely vicenin-2 and scolymoside, were examined for its effects on inflammatory responses by monitoring the effects of vicenin-2 and scolymoside on lipopolysaccharide (LPS)-mediated vascular inflammatory responses.

Methods: The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability,monocytes adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated HUVECs and mice.

Results: We found that post-treatment of each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced endothelial cell protein C receptor (EPCR)shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore,each compound suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, posttreatment with each compound resulted in reduced LPS-induced lethal endotoxemia.

Conclusions: Vicenin-2 and scolymoside possess anti-inflammatory functions by inhibiting hyperpermeability,expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.